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appeared 4 February 1999
Relationship Between Copper and Iron Metabolism Offers
Insight into Iron Deficiency Anemia
Hephaestus, the Greek god of metal-working, wove a net of iron, and
ensnared the illicit lovers Ares and Aphrodite making love. Now, centuries later, a newly
discovered protein that bears his name is playing an equally revelatory role, exposing an
intimate relationship between copper and iron metabolism, and offering researchers an
important insight into a cause of iron deficiency anemia.
The discovery of the Hephaestin gene -- and the protein it encodes -- was made by a team
led by researchers at UCSF, in a laboratory high on the hill of Parnassus Ave. It is
reported in the February issue of Nature Genetics.
The researchers discovered the Hephaestus gene in mice with iron deficiency anemia, and
determined that the protein facilitates transport of iron from the intestines into the
body's circulatory system. When the gene is mutated, as it is in the mice, iron cannot be
transported to the blood, and iron deficiency anemia occurs.
A like gene exists in humans, thereby offering insight into a condition that affects as
much as 25 percent of the world's population. More broadly, Hephaestus' discovery offers
insight into the overall pathway of iron transport, which follows an intricate three-step
path in the body, moving from the intestines through to the circulatory system. A greater
understanding of the pathway could shed light on the numerous clinical problems that can
develop as a result of iron overload, as well as iron deficiency.
Also, the discovery could solve a conundrum that has long puzzled researchers: why
supplements of copper, as well as iron, are required to reverse iron deficiency anemia.
The Hephaestin gene, the researchers discovered, produces a copper-bound protein with
enzymatic activity that is able to change the valence of iron from its armored state in
what is called "iron 2" to its bioavailable state of "iron 3" thereby
making available to the body a metal that the ancient Greeks so valued that they enshrined
it in a deity.
"We've identified one of the key components of the whole iron uptake system,"
said the lead author of the study, Christopher Vulpe, who led the study as a postdoctoral
fellow in the laboratory of Jane Gitschier, a professor of medicine and pediatrics at
UCSF, a Howard Hughes Medical Institute Investigator and a senior author of the study.
The reason the investigators pursued the question of iron transport is because iron is
essential to the life of all living species. It is a constituent of hemoglobin, the
protein that carries oxygen to every tissue in the body, and is so valued that the body
harbors what it receives, having no physiologic mechanism for excreting the element except
through the blood loss. Still, organisms must utilize elaborate molecular mechanisms for
the extraction, mobilization and utilization of the metal, which can only be obtained
through diet or supplements.
While many cases of iron deficiency anemia occur as a result of inadequate diet or blood
loss, genetic defects in mechanisms involved in iron transport at various stages in the
pathway may contribute to susceptibility to anemia, said Vulpe.
"More work needs to be done to determine if and how often genetic defects in iron
transport occur in humans," said Gitschier.
Links:
Full press release
Nature Genetics
Source: Jennifer O'Brien, News
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